The NPA theory shows a clear reason for that. In the case of COMT val/met polymorphism, while it should show causation in well done research for schizophrenia it doesn't. The reason is clear when looking at the NPA frequencies in any given population. For example if a study is done in the southern USA, some individuals with COMT met/met would have both N and A traits, some few with P trait also. So only those with COMt met met without A trait would have a significantly higher incidence of schizophrenia, thus confounding the association. In an almost 100% sanguine habitancy, theoretically COMT met/met should be significantly associated with schizophrenia and with autism.
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